The general goal of the projected research is to arrive at an understanding of the mode of action of glucocorticoids at molecular and cellular levels and at the level of the whole organism. Central to our investigations will be an intensive study of the mechanisms of glucocorticoid action of lymphocytes, particular rat and mouse thymocytes in isolation. We will also study the actions of glucocorticoids on macrophages and on cell-mediated immune reactions. These actions of glucocorticoids are of great importance owing to their applications in immunosuppression, in the treatment of lymphocytic leukemia and their relation to anti-inflammatory effects, and because they provide the most striking example of the general catabolic effects of glucocorticoids on peripheral tissues. Our work is based on our previous studies demonstrating that thymus cells contain glucocorticoid receptors and respond rapidly to glucocorticoids in vivo and in vitro with a decrease in glucose uptake. This effect appears to be mediated by induction of RNA followed by induction of a protein that inhibits glucose transport. One of our specific goals will be to identify this hypothetical protein directly. Another will be to map the changes in proteins and other molecules that take place in various cell structures as the actions of glucocorticoids progress to cytolysis.